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Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside

  • Skin Cancer (BY Kwong, Section Editor)
  • Published:
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Opinion statement

Cutaneous T cell lymphomas (CTCLs) are non-Hodgkin lymphomas of skin homing T cells. Although early-stage disease may be limited to the skin, tumor cells in later stage disease can populate the blood, the lymph nodes, and the visceral organs. Unfortunately, there are few molecular biomarkers to guide diagnosis, staging, or treatment of CTCL. Diagnosis of CTCL can be challenging and requires the synthesis of clinical findings, histopathology, and T cell clonality studies; however, none of these tests are entirely sensitive or specific for CTCL. Treatment of CTCL is often empiric and is not typically based on specific molecular alterations, as is common in other cancers. In part, limitations in diagnosis and treatment selection reflect the limited insight into the genetic basis of CTCL. Recent next-generation sequencing has revolutionized our understanding of the mutational landscape in this disease. These analyses have uncovered ultraviolet radiation and recombination activating gene (RAG) endonucleases as important mutagens. Furthermore, these studies have revealed potentially targetable oncogenic mutations in the T cell receptor complex, NF-κB, and JAK-STAT signaling pathways. Collectively, these somatic mutations drive lymphomagenesis via cancer-promoting changes in proliferation, apoptosis, and T cell effector function. We expect that these genetic findings will launch a new era of precision medicine in CTCL.

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Authors and Affiliations

  1. Department of Dermatology, Yale University School of Medicine, 333 Cedar Street, LCI 501, PO Box 208059, New Haven, CT, USA

    William E. Damsky MD, PhD

  2. Department of Dermatology and Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Robert H Lurie Medical Research Center, Suite 5-115, 303 E Superior St., Chicago, IL, USA

    Jaehyuk Choi MD, PhD

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  1. William E. Damsky MD, PhD
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  2. Jaehyuk Choi MD, PhD
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Correspondence to Jaehyuk Choi MD, PhD.

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William E. Damsky and Jaehyuk Choi declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Skin Cancer

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Damsky, W.E., Choi, J. Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside. Curr. Treat. Options in Oncol. 17, 33 (2016). https://doi.org/10.1007/s11864-016-0410-8

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  • DOI: https://doi.org/10.1007/s11864-016-0410-8

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